[unreadable] The long-range goal of this competing continuation grant is to assess and improve the breast tumor diagnostic capabilities of diffuse optical tomography with near infrared light. Near-infrared diffuse optical tomography is based on the study of functional processes, and provides several unique measurable parameters with potential to enhance breast tumor sensitivity and specificity. The techniques utilize non-ionizing radiation, are non-invasive, and are technologically simple and fast. Tissue optical absorption coefficients provide access to blood dynamics, total hemoglobin concentration, blood oxygen saturation, water concentration and lipid content. These tissue properties are often substantially different in rapidly growing tumors. During this proposal cycle we assembled a parallel-plate soft-compression apparatus for diffuse optical tomography of breast, and we have began pilot clinical studies with the instrument at the Hospital of the University of Pennsylvania. Our pilot studies have clearly shown tumors are detectable and characterizable with the diffuse optical method; they can even be tracked during neoadjuvant chemotherapy. Our proposed work emphasizes hardware and software improvements, and then pushes for more and deeper clinical studies. In particular we will upgrade the source switching apparatus and detection CCD in order to improve speed by approximately a factor of 4. This will increase our spectral coverage by approximately 4, given the same measurement time. We will upgrade the breast table to improve our idefinition of tissue boundaries and increase our sensitivity to breast tissue near the chest wall. We will upgrade our software for reconstruction in many ways, but most importantly in ways that reduce artifacts near boundaries. We will continue pilot studies on normal subjects and tumor bearing patients, this time with more specific supporting information from radiologists and pathologists, and finally, we will have a unique opportunity to follow a group of patients undergoing neoadjuvant chemotherapy. If successful, these powerful new improvements will enhance the fidelity of the breast images, and the anatomical and functional information generated by the device will improve our ability to detect and specify the nature of breast tumors. [unreadable] [unreadable]